The detection and quantitative determination of particles is important in the areas of preventive and diagnostic medicine. The particles may be single eukaryotic cells with particular properties, bacteria, viruses, protein aggregates, or other molecular entities. We have built a prototype instrument that combines a novel fluorescence technique with filtration algorithms based on particle passage pattern recognition. It has allowed the detection of particles in turbid fluids down to a few per millimeter in short scanning times. This proposal has the Specific Aims of expanding this technology and applying it to the measurement and characterization of ultra-low abundance multimers of the Amyloid beta in clinical fluids. Oligomeric forms of this peptide are a potential molecular marker to quantify disease progression in Alzheimer's disease and to identify persons at risk for age-related cognitive change and dementia. This proposal also seeks to optimize sample treatment, instrumental parameters, data analysis and assay methods to rapidly quantify and determine the physical properties of the oligomers. The technology could potentially be extended to the diagnosis and therapeutic monitoring of other protein aggregation/misfolding neurologic diseases. [unreadable] [unreadable]